APOBECfamily

APOBEC family refers to a group of zinc-dependent cytidine deaminases that catalyze the deamination of cytosine to uracil in single-stranded DNA or RNA. This editing can introduce mutations in DNA or alter RNA transcripts, contributing to innate immune defense against pathogens as well as to endogenous regulatory processes. Members of the family vary in substrate preference, tissue distribution, and biological role, and the repertoire includes several well-studied enzymes and a number of less characterized relatives.

In humans, the best characterized members include APOBEC1, APOBEC2, APOBEC3 (a subfamily with multiple paralogs: A3A, A3B, A3C, A3D, A3F, A3G, A3H, among others) and APOBEC4. APOBEC1 is renowned for editing ApoB mRNA in the intestine, converting a cytidine to uridine and generating a truncated protein (ApoB-48) in a tissue-specific manner that depends on cofactors such as the APOBEC1 complementation factor (ACF). The APOBEC3 subfamily plays a central role in antiviral defense, targeting retroelements and many viruses by deaminating cytosine in single-stranded DNA formed during reverse transcription, leading to C-to-U changes that become G-to-A mutations in the viral genome. Viral countermeasures, such as HIV-1 Vif, can inhibit APOBEC3 activity.

APOBEC enzymes are also implicated in cancer biology. Activity of APOBEC3A and especially APOBEC3B can generate characteristic mutational signatures (often referred to as APOBEC signatures SBS2 and SBS13) in somatic genomes, contributing to kataegis and tumor evolution. Overall, the APOBEC family integrates roles in RNA/DNA editing, antiviral immunity, and genome mutagenesis.